Pyrrolidin derivative.



ALBRECHT THIELE, 0F BERLIN, GERMANY, ASSIGNOR T0 CHEMISCHE FABRIK .AUF

ACTIEN (VORM'. E. SCHERING), OF BERLIN, GERMANY.

PYRROLIDIN DERIVATIVE.

No Drawing.

To all whom it may concern Be it known that I, ALBRECHT TI-IIELE, doctorof philosophy, chemist, citizen of the German Empire, residing atBerlin, Kingdom of Prussia, Empire of Germany, have invented a new anduseful Improvement in Pyrrolidin Derivatives, of which the following isa specification.

The subject matter of this invention is new pyrrolidin derivatives whichmay be useful in therapeutics.

.The new compounds may be obtained by condensing with or without asolvent, an acidylated pyroracemic acid ester either: (1) withbenzaldehyde and a substituted anilin, (2) with a substitutedbenzaldehyde and anilin or a substituted anilin, (3) with benzaldehydeand heterocyclic compounds, ,or (4:) with heterocyclic aldehydes andamins.

The new pyrrolidin derivatives are insoluble in water, more or lesseasily soluble in alcohol, difiicultly soluble in ether and benzene,soluble in a-lkalis and are stable when heated with dilute acids andalkalis. Their alcoholic solutions assume a dark red color upon theaddition of ferric chlorid.

The new compounds may be represented by the following general formula:

00 CH-CO-R Examples.

(1.) 106 parts of m-toluidin are heated with 106 parts benzaldehyde fora quar ter of an hour on a water bath, 160 parts of ascetylpyroracemicacidethylester being heated in an absolute alcoholic solution for aquarter of an hour upon a water bath. 242

Patented Aug. 3,1915.

Application filed November 14, 1913. Serial No. 801,074.

0G 4 CH.COCH

N.C5H4(CH3) ortho 106 parts o-toluidin and 106 parts benzaldehyde aredissolved in 1000 parts of ether, treated with 158 parts ofacety1pyroracemic acidester and allowed to stand for 21 hours. After theaddition of a 5% soda solution the ether is distilled off and theresulting compound purified through its sodium salt. It crystallizesfrom a mixture of benzene, petrol and ether in rose colored crystalswhich melt at 177-17 9 C.

(4.) The manufacture of l-o-mcthowyighcnyl 2-phcuyZ-S-acetyZ-4.5-di7cctopyrroli 0C CHUOCH 122 parts of anisidin and106 parts of benzaldehyde are allowed to stand with 158 partsacetylpyroracemic acid ester for twenty four hours. The above resultingcompound after purification and recrystallization from 96% alcohol meltsand decomposes at 225227 G.

(5.) The manufacture ofJ-phenyZ-Q-pipcronyZ-3-acetyZ-46-dihctopyrrolidim- 92 parts anilin and150 parts piperonal are heated for some hours in benzene w1th 158 partsacetylpyroracemic acidesten. After purification and recrystallizationfrom 96% alcohol the pyrrolidin derivative above named is obtained whichmelts at 197 C.

(6.) The manufacture of l-p-tclyZ-Q-p-dimiatilq laminophenyl 3 aeetgl-tfi-dz'kctcpg rre a m.' a

para

158 parts of acetylpyroracemic acidester are caused to react upon 144parts of 8- aminoquinolin and 106 parts of benzaldehyde mixed withbenzene. After purification the above named product is obtained whichmelts anddecomposes at 222 C.

(8.) The manufacture of 1- (I-pkeng Z-QB- d'imethyl 5 pyrazolyl) -2-phenyl -3-acctyl 4.5 diketopyrrolidtn.

t c.cn3 l CHCOGH;

CHCOCHa 00 mm g 61 parts of phenyldimethylaminopyrazolone together with32 parts of benzaldehyde and 50 parts acetylpyroracemic acidester aredissolved in 500 parts benzene and heated to 100110 C. for 5 to 6 hoursin a tube.

After purification the compound appears as a light brown powder whichgradually decomposes at moreelevated temperatures. It has abitter taste;gives a brown red coloration when treated with ferric chlorid and issoluble inorganic solvents with the excelption of ether and a mixture ofpetrol and et er.

(9.) The, manufacture cfLPkeny Z-Q-fuT furyL3-acetyZ-4.5-dilcet0pyrrolidim- 0c c ncocm i onocina v 96 partsfurfurol 158 parts acetylpyrora-.

cemic acidester and 93 parts anilin are dissolved in 1000 parts benzeneand after standing for many hours" heated for two hours upon a waterbath. After purification the above compound is obtained whichrecrystallized from benzene or 40% alcohol forms yellow-green crystals.These melt and decompose at 190 0. They dissolve in alcohol and withdifliculty in ether.

.(10.) The manufacture of l-c-metkomyghenyZ-Z-phenyl- 3-benzoyl-4. 5dtketopyrrcli- 00 CHCOCaHs oc CHCsHs 110 parts benzoylpyroracemicacidester dissolved in benzene are allowed to react upon- 55 partsbenzaldehyde and 65 parts o-anisidin for 24 hours. Afterrecrystallization from 50% alcohol crystals are obtainedwhich becomesoft at about 205- C. and melt and decompose at 215-217 C.

I claim as my invention:

As new products the herein described diketo-pyrrolidin derivatives, thesame being condensation products of an acidylated pyroracemic acidester'with aldehydes and amins and being insoluble in water, more orless easily soluble in alcohol, diflicultly soluble in ether andbenzene, soluble in alkalis and being stable when heated with diluteacids and alkalis, substantially as set forth.

In testimony whereof I have hereunto set my signature in the presence oftwo subscribing witnesses.

DR. ALBRECHT THIELE.

Witnesses WOLDEMAR HAD-PT, HENRY HASPER.

